Skip to main content

Advertisement

Log in

Unlike in clear cell renal cell carcinoma, KRAS is not mutated in multilocular cystic clear cell renal cell neoplasm of low potential

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The recent International Society Urological Pathology (ISUP) Vancouver classification of renal neoplasia distinguishes between clear cell renal cell carcinoma (CCRCC) and multilocular cystic clear cell renal cell neoplasm of low malignant potential (mcCCRCNLMP). Current data supports the latter being a low aggressive neoplasm which does not recur or metastasize after definitive surgical treatment. Therefore, differentiating mcCCRCNLMP from low-grade CCRCC with cystic changes is important for patient management. The role of the pathologist is crucial in distinguishing between both entities. Since these tumors have overlapping molecular features, including 3p deletion and VHL mutations, it would be potentially clinically relevant to identify other molecular differences which might help to differentiate between these entities. We studied six different codons of KRAS and six codons of NRAS in mcCCRCNLMP and CCRCC of low grade and stage. All cases of CCRCC had a mutation in one of the studied KRAS codons. In contrast, no mutations were found in mcCCRCNLMP. We provide preliminary data to support that CCRCC and mcCCRCNLMP, in spite of their histologic similarity, show a different pattern of KRAS gene mutation, which is consistent with the observed differences in disease progression between these tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Srigley JR, Delahunt B, Eble JN, Egevard L, Epstein JI, Grignon D, Hes O, Moch H, Montironi R, Tickoo SK, Zhou M, Argani P (2013) The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Am J Surg Pathol 37:1469–1489

    Article  PubMed  Google Scholar 

  2. Williamson SR, Halat S, Eble JN, Grignon DJ, Lopez-Beltran A, Montironi R, Tan PH, Wang M, Zhang S, Maclennan GT, Baldridge LA, Cheng L (2012) Multilocular Cystic renal Cell Carcinoma: Similarities and Differences in Immunoprofile Compared with Clear Cell Renal Cell Carcinoma. Am J Surg Pathol 36:1425–1433

    Article  PubMed  Google Scholar 

  3. Williamson SR, MacLennan GT, Lopez-Beltran A, Montironi R, Tan PH, Martignoni G, Grignon DJ, Eble JN, Idrees MT, Scarpelli M, Cheng L (2013) Cystic partially regressed clear cell renal cell carcinoma: a potential mimic of multilocular cystic renal cell carcinoma. Histopathology 63:767–779

    Article  PubMed  Google Scholar 

  4. Mazzucchelli R, Scarpelli M, Montironi R, Cheng L, Lopez-Beltran A (2012) Multilocular cystic renal cell neoplasms of low malignant potential. Anal Quant Cytopathol Histopathol 34:235–258

    Google Scholar 

  5. Halat S, Eble JN, Grignon DJ, Lopez-Beltran A, Montironi R, Tan PH, Wang M, Zhang S, MacLennan GT, Cheng L (2010) Multilocular cystic renal cell carcinoma is a subtype of clear cell renal cell carcinoma. Mod Pathol 23:931–936

    Article  PubMed  Google Scholar 

  6. Mazzucchelli R, Galosi AB, Scarpelli M, Lopez-Beltran A, Cheng L, Montironi R (2014) Contemporary update on pathology-related issues of adult renal neoplasms. Anal Quant Cytopathol Histopathol 36:1–8

    Google Scholar 

  7. Shuch B, Amin A, Armstrong AJ, Eble JN, Ficarra V, Lopez-Beltran A, Martignoni G, Rini BI, Kutikov A (2015) Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity. Eur Urol 67:85–97

    Article  PubMed  Google Scholar 

  8. Lopez-Beltran A, Cheng L, Vidal A, Scarpelli M, Kirkali Z, Blanca A, Montironi R (2013) Pathology of renal cell carcinoma: an update. Anal Quant Cytopathol Histopathol 35:61–76

    Google Scholar 

  9. Kuroda N, Ohe C, Mikami S, Inoue K, Nagashima Y, Cohen RJ, Pan CC, Michal M, Hes O (2012) Multilocular cystic renal cell carcinoma with focus on clinical and pathobiological aspects. Histol Histopathol 27:969–974

    PubMed  Google Scholar 

  10. Cheng L, Williamson SR, Zhang S, Maclennan GT, Montironi R, Lopez-Beltran A (2010) Understanding the molecular genetics of renal cell neoplasia: implications for diagnosis, prognosis and therapy. Expert Rev Anticancer Ther 10:843–864

    Article  CAS  PubMed  Google Scholar 

  11. Cheng L, Zhang S, MacLennan GT, Lopez-Beltran A, Montironi R (2009) Molecular and cytogenetic insights into the pathogenesis, classification, differential diagnosis, and prognosis of renal epithelial neoplasms. Hum Pathol 40:10–29

    Article  CAS  PubMed  Google Scholar 

  12. McGrath JP, Capon DJ, Smith DH, Chen EY, Seeburg PH, Goeddel DV, Levinson AD (1983) Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene. Nature 304:501–506

    Article  CAS  PubMed  Google Scholar 

  13. Popescu NC, Amsbaugh SC, Di Paolo JA, Tronick SR, Aaronson SA, Swan DC (1985) Chromosomal localization of three human ras genes by in situ molecular hybridization. Somat Cell Mol Genet 11:149–155

    Article  CAS  PubMed  Google Scholar 

  14. Kranenburg O (2005) The KRAS oncogene: past, present, and future. Biochim Biophys Acta 1756:81–82

    CAS  PubMed  Google Scholar 

  15. Delahunt B, Cheville JC, Martignoni G, Humphrey PA, Magi-Galluzzi C, McKenney J, Egevad L, Algaba F, Moch H, Grignon DJ, Montironi R, Srigley JR, Members of the ISUP Renal Tumor Panel (2013) The international society of urological pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. Am J Surg Pathol 37:1490–1504

    Article  PubMed  Google Scholar 

  16. Trpkov K, Grignon DJ, Bonsib SM, Amin MB, Billis A, Lopez-Beltran A, Samaratunga H, Tamboli P, Delahunt B, Egevad L, Montironi R, Srigley JR, Members of the ISUP Renal Tumor Panel (2013) Handling and staging of renal cell carcinoma: the international society of urological pathology consensus (ISUP) conference recommendations. Am J Surg Pathol 37:1505–1517

    Article  PubMed  Google Scholar 

  17. Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386

    CAS  PubMed  Google Scholar 

  18. Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S, Saha S, Markowitz S, Willson JK, Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE (2003) Mutational analysis of the tyrosine kinome in colorectal cancers. Science 300:949

    Article  CAS  PubMed  Google Scholar 

  19. Montironi R, Mazzucchelli R, Scarpelli M, Lopez-Beltran A, Cheng L (2013) Update on selected renal cell tumors with clear cell features with emphasis on multilocular cystic clear cell renal cell carcinoma. Histol Histopath 28:1555–1566

    CAS  Google Scholar 

  20. Suzigan S, López-Beltrán A, Montironi R, Drut R, Romero A, Hayashi T, Gentili AL, Fonseca PS, deTorres I, Billis A, Japp LC, Bollito E, Algaba F, Requena-Tapias MJ (2006) Multilocular cystic renal cell carcinoma: a report of 45 cases of kidney tumor of low malignant potential. Am J Clin Pathol 125:217–222

    Article  PubMed  Google Scholar 

  21. Moch H (2010) Cystic renal tumors: new entities and novel concepts. Adv Anat Pathol 17:209–214

    Article  PubMed  Google Scholar 

  22. You D, Shim M, Jeong IG, Song C, Kim JK, Ro JY, Hong JH, Ahn H, Kim CS (2011) Multilocular cystic renal cell carcinoma: clinicopathological features and preoperative prediction using multiphase computer tomography. BJU Int 108:1444–1449

    Article  PubMed  Google Scholar 

  23. Von Teichman A, Comperat E, Behnke S, Storz M, Moch H, Schraml P (2011) VHL mutations and dysregulation pf pVHL- and PTEN-controlled pathways in multilocular cystic renal cell carcinoma. Mod Pathol 24:571–578

    Article  Google Scholar 

  24. Yang L, Wu Q, Xu L, Zhang W, Zhu Y, Liu H, Xu J, Gu J (2015) Increased expression of colony stimulating factor-1 is a predictor of poor prognosis in patients with clear-cell renal cell carcinoma. BMC Cancer 15:67–78

    Article  PubMed Central  PubMed  Google Scholar 

  25. Algaba F, Akaza H, Lopez-Beltran A, Martignoni G, Moch H, Montironi R, Reuter V (2011) Current pathology keys of renal cell carcinoma. Eur Urol 60:634–643

    Article  PubMed  Google Scholar 

  26. Stamatiou KN, Sofras F (2009) Multilocular cystic nephoma and multicystic clear cell carcinoma: two faces of the Roman god Janus? Int J Surg Pathol 17:170–171

    Article  PubMed  Google Scholar 

  27. Chen YN, Tickoo SK (2012) Spectrum of preneoplastic and neoplastic cystic lesions of the kidney. Arch Lab Pathol Med 136:400–409

    Article  Google Scholar 

  28. Sinicrope FA, Shi Q, Smyrk TC, Thibodeau SN, Dienstmann R, Guinney J, Bot BM, Tejpar S, Delorenzi M, Goldberg RM, Mahoney M, Sargent DJ, Alberts SR (2015) Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology 148:88–99

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria Rosaria Raspollini.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raspollini, M.R., Castiglione, F., Martignoni, G. et al. Unlike in clear cell renal cell carcinoma, KRAS is not mutated in multilocular cystic clear cell renal cell neoplasm of low potential. Virchows Arch 467, 687–693 (2015). https://doi.org/10.1007/s00428-015-1859-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-015-1859-8

Keywords

Navigation